U.S. patent application number 14/481650 was filed with the patent office on 2014-12-25 for active ingredient delivery system.
This patent application is currently assigned to FIRMENICH SA. The applicant listed for this patent is FIRMENICH SA. Invention is credited to Christopher M. GREGSON, Matthew P. SILLICK.
Application Number | 20140377364 14/481650 |
Document ID | / |
Family ID | 42260321 |
Filed Date | 2014-12-25 |
United States Patent
Application |
20140377364 |
Kind Code |
A1 |
GREGSON; Christopher M. ; et
al. |
December 25, 2014 |
ACTIVE INGREDIENT DELIVERY SYSTEM
Abstract
A spray-chilled particulate delivery system that has a
crystalline matrix structure and comprises a volatile hydrophobic
active ingredient and a carrier material selected from the group
consisting of erythritol and mannitol and mixtures thereof wherein,
relative to the total weight of the carrier material, 75% or more
of the carrier material is in crystalline form. The process for
preparing the delivery system comprises the steps of (i) forming a
melt of a carrier material selected from the group consisting of
erythritol and mannitol and mixtures thereof (ii) incorporating a
volatile hydrophobic active ingredient into the melt (iii) forming
a melt-mixture comprising an emulsion, dispersion or suspension of
the volatile hydrophobic active ingredient in the melt (iv) forming
discrete particles of the melt mixture, and (v) cooling the
discrete particles, so as to form the crystalline delivery
system.
Inventors: |
GREGSON; Christopher M.;
(Princeton, NJ) ; SILLICK; Matthew P.;
(Plainsboro, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
FIRMENICH SA |
Geneva |
|
CH |
|
|
Assignee: |
FIRMENICH SA
Geneva
CH
|
Family ID: |
42260321 |
Appl. No.: |
14/481650 |
Filed: |
September 9, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13509901 |
May 15, 2012 |
8828441 |
|
|
PCT/IB2010/055938 |
May 26, 2011 |
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14481650 |
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Current U.S.
Class: |
424/490 ;
424/489; 426/3; 426/5; 426/548; 514/78 |
Current CPC
Class: |
A23V 2200/224 20130101;
A23P 10/30 20160801; A23G 4/06 20130101; A23L 27/10 20160801; A23V
2002/00 20130101; A23L 27/70 20160801; A61K 47/10 20130101; A23P
10/20 20160801; A23G 4/20 20130101; A23V 2250/6418 20130101; A23G
3/36 20130101; A61K 9/1623 20130101; A23V 2002/00 20130101; A23V
2250/6418 20130101; A23L 29/37 20160801; A23V 2250/6402 20130101;
A23V 2200/224 20130101; A23V 2002/00 20130101; A23V 2250/6402
20130101; A23L 27/72 20160801; A23V 2200/224 20130101; A61K 31/685
20130101; A23V 2002/00 20130101 |
Class at
Publication: |
424/490 ;
424/489; 514/78; 426/548; 426/3; 426/5 |
International
Class: |
A61K 47/10 20060101
A61K047/10; A23L 1/221 20060101 A23L001/221; A23G 3/36 20060101
A23G003/36; A61K 31/685 20060101 A61K031/685 |
Claims
1. A spray-chilled particulate delivery system, the particulate
delivery system comprising a crystalline structure and comprising
(i) a carrier material selected from the group consisting of
erythritol and mannitol and mixtures thereof, and (ii) a volatile
hydrophobic active ingredient that is liquid at wherein, relative
to the total weight of the carrier material, 75% or more of the
carrier material is in crystalline form.
2. The delivery system according to claim 1 wherein the carrier
material is erythritol.
3. The delivery system according to claim 1 wherein the active
ingredient is, at least partly, included within crystals of the
carrier material.
4. The delivery system according to claim 1, wherein the particles
have an average means diameter of 5 to 4000 microns.
5. The delivery system according to claim 1 having a freely settled
density of 0.7 g cm.sup.-3 to 1.35 g cm.sup.-3.
6. The delivery system according to claim 1 wherein the active
ingredient is liquid, when measured at 45.degree. C. and 1
atmosphere.
7. A process for preparing a particulate delivery system having a
crystalline structure comprising the steps of: (i) forming a melt
of a carrier material selected from the group consisting of
erythritol and mannitol, (ii) incorporating a volatile hydrophobic
active ingredient into the melt, (iii) forming a melt-mixture
comprising an emulsion, dispersion, solution or suspension of the
volatile hydrophobic active ingredient in the melt, (iv) forming
discrete particles of the melt mixture, and (v) cooling the
discrete particles, so as to form a particulate delivery system in
which, relative to the total weight of the carrier material, 75% or
more of the carrier material is in crystalline form.
8. A process according to claim 7 wherein the melt-mixture of step
(ii) is supercooled prior to forming the discrete particles in step
(iii).
9. A process according to claim 7 wherein the melt-mixture of step
(iii) comprises 10 wt % or less of water, relative to the total
weight of the melt mixture.
10. A process according to claim 7 wherein the cooling step
comprises heat removal at a rate of greater than about 600
kJ.kg.sup.-1.min.sup.-1.
11. A process according to claim 7 wherein the particulate delivery
system is further encapsulated.
Description
[0001] This application is a continuation application of U.S.
patent application Ser. No. 13/509,901 filed Dec. 6, 2012 which is
a 371 filing of International Patent Application PCT/IB2010/055938,
filed Dec. 20, 2010 which claims priority from U.S. Provisional
Application No. 61/288,921 filed Dec. 22, 2012 and from European
Patent No.: 091807198.8, filed Dec. 24, 2009.
TECHNICAL FIELD
[0002] The present invention relates to a delivery system for
active ingredients. It also relates to a process for preparing such
a delivery system.
BACKGROUND AND PRIOR ART
[0003] Delivery systems or encapsulation systems are used in
various industries to protect active ingredients or to control
their release. For instance, in the food industry they are often
used to protect flavors, in particular against losses of volatile
components (i) during storage prior to incorporation into the food
products, (ii) during mixing of the flavor component with the other
food ingredients, (iii) during food processing, such as cooking and
baking, (iv) during transportation and storage and (v) during the
preparation of the food product by the end-consumer.
[0004] Similarly, in the nutraceutical industry, they are often
used to protect oxygen-sensitive active material, such as fish oils
rich in polyunsaturated fatty acids, by providing an oxygen bather
around the material.
[0005] In the flavor and fragrance industry it is known to
encapsulate flavors and perfumes so that their release can be
controlled according to the needs of the end application.
[0006] In all of these applications, the delivery system has the
primary object of protecting the sensitive or volatile active
ingredient against, for instance, evaporation, degradation or
migration, or delaying the release rate of the active ingredient
into a desired medium.
[0007] Various delivery systems are known that achieve one or more
of these object, such as extruded granular delivery systems, for
instance. Extruded systems are often formed by melt-extrusion and
typically comprise a matrix material or carrier material for a
material, product or ingredient that is encapsulated. The matrix
material is often described as "viscous" or "rubbery" during the
extrusion process and "glassy" in the finished product.
[0008] It is recognised by many experts in the field that, in the
glassy state, all molecular translation is halted and it is this
which provides effective entrapping of the flavor volatiles and
prevention of other chemical events such as oxidation. Conversely,
in the viscous state, the encapsulation of materials, products and
ingredients is less effective in preventing leakage of the
encapsulated material.
[0009] Thus, glassy matrices have to be produced very carefully to
achieve the desired properties.
[0010] As an alternative to glassy matrices, it is known to
encapsulate active ingredients using crystalline matrices. A well
documented process for crystalline encapsulation is
co-crystallisation in which an active ingredient becomes embedded
in a agglomerate of macro- or microscopic crystals. Numerous
publications describing this technology exist, such as Zeller et
al., Trends in Food Science & Technology 9 (1999) 389-94;
Madene et al. International Journal of Food Science &
technology 41 (2006) 1-21); Food Technology, 47, 146-148 (1993);
Food Technology, 42, 87-90. 1988; and International Sugar Journal,
96, 493-494. 1994.
[0011] U.S. Pat. No. 4,338,350 (Chen et al) describes
co-crystallization and refers to concentrating a sucrose solution
to the range of 95 to 97%, cooling slightly to create a
supersaturated solution, mixing in a second active ingredient (such
as a flavor oil), and then vigorously agitating the mixture to
cause the sucrose to spontaneously crystallize with the inclusion
or entrapment of the active. Thus in this process, crystallization,
conglomerate formation, active entrapment, and water volatilization
all occur more or less simultaneously within the agitation step
making the overall process more difficult to control and
optimize.
[0012] This difficulty is recognised in Food Technology, 42, 87-90.
1988 where it is stated that the process requires proper control of
the rates of nucleation and crystallization, and thermal balance
during all of the various phases of the process
[0013] A similar co-crystallization process for encapsulated orange
peel oil is also disclosed in LWT--Food Science and Technology 29,
645-647, 1996. This describes how 100 g to 250 g of orange peel oil
can be incorporated per kg of sugar but that, while the product is
granular and easy to handle, the flavor oxidizes readily on
subsequent storage and addition of an antioxidant is necessary to
protect the flavor. The porous structure of the agglomerates
apparently leads to flavor oxidation.
[0014] Thus, it would be desirable to provide a crystalline
encapsulation system which addresses one or more of these
drawbacks. It would be especially desirable to increase the ability
to control the process more precisely. It would also be desirable
to avoid or at least minimise the porosity of the structure so as
to better protect labile or sensitive active ingredients.
[0015] Other crystalline entrapments systems are also known. For
instance, U.S. Pat. No. 2,566,410 (Griffin) describes a process for
creating a solidified composition of a continuous crystalline
sorbitol phase and a dispersed essential oil phase. The essential
oil is described as "so thoroughly coated and entrapped that loss
of said oil from the mass occurred at a negligible rate." However,
unseeded crystallization of sorbitol is known to be a time
consuming process taking up to several days (Szatisz J. Therm.
Anal. 12 (1977) 351-360) which is an obvious drawback for any
commercial application.
[0016] U.S. Pat. No. 2,904,440 (Dimick et al) also relates to
sorbitol encapsulation where the water and low molecular weight
alcohols are removed from a flavoring agent prior to incorporation
in molten sorbitol. This is said to remove constituents that
interfere in the crystallization process and extend the use of the
technology to other systems such as fruit essences. However, this
requires additional steps in the process. Further, the sorbitol
melt needs to be supercooled prior to adding flavor and seed
crystals. Finally, the solidified product needs to be ground into
granular particles.
[0017] U.S. Pat. No. 4,388,328 (Glass) employs a mixture of
sorbitol, saccharine and mannitol as the entrapping medium.
Mannitol and saccharin are believed to lower the crystallization
temperature of sorbitol to below 70.degree. C. rendering the
process advantageous for incorporating volatile flavor compounds.
The melt-emulsion could be cast while liquid as a sheet or formed
into tablets or droplets with a mold. To create smaller particles
solidified sheets are ground and passed through a mess screen.
[0018] EP1013176 (Gergely) relates to sugar/polyols matrices for
the encapsulation of solids and liquids. However, GDL is used at
high levels (10 to 50%) to suppress crystallization and so relates
to amorphous glassy carbohydrate matrices rather than crystalline
delivery systems. Furthermore, the particles are formed by
grinding.
[0019] U.S. Pat. No. 5,075,291 (Duross) describes the use of
polyols for creating solid dispersions of pharmaceutical actives.
The particles are formed by grinding.
[0020] Generating particles by grinding inevitably leads to a loss
of active ingredient at the surface where ground and so it would be
desirable to address this problem.
[0021] U.S. Pat. No. 6,083,438 describes a process for preparing a
composition suitable for use as an excipient for tabletting
comprising following steps of (a) mixing of erythritol and sorbitol
in a dry form, (b) heating to a temperature where the mixed
products are melted, (c) cooling the product, (d) milling the
cooled product to obtain a composition having a desired particle
size. Milling suffers from the same drawbacks as grinding.
[0022] It is also known to use mannitol, a typically crystalline
material, in flavor encapsulation. In U.S. Pat. No. 3,314,803 (Dame
et al) acetaldehyde is incorporated into mannitol solids through
spray drying a super-saturated solution of mannitol. However, this
process requires great care in drying the super-saturated solution
to avoid completely volatilizing the acetaldehyde or forming a
non-entrapping dried mannitol composition. In EP-A1-0497439,
erythritol is spray-dried to provide conveniently sized crystals in
the form of a free-flowing powder.
[0023] However, in both cases, such heating is potentially
detrimental since it encourages the loss of volatile active
ingredients.
[0024] U.S. Pat. No. 3,341,415 (Morton) discloses the combination
of mannitol with other sugars or sugar alcohols to form a carrier
for pharmaceutical actives. Pharmaceutical actives are typically
non volatile and so this document does not address the issue of how
to effectively encapsulate volatile liquid ingredients.
[0025] It would thus be desirable to address this problem.
[0026] Encapsulation of active ingredients by spray chilling is
described in U.S. Pat. No. 5,525,367 where the carrier for the
active ingredient is a high melting-point edible solid such as a
hydrogenated vegetable oil, a stearin, or an edible wax. However,
such carriers do not always provide a sufficient barrier to prevent
hydrophobic active ingredients from leaking from the capsules.
[0027] In US-A1-2009/0142401 (Appel et al) spray-congealing is used
to form multiparticles of low-solubility drugs and carriers that
result in rapid release of the drug. The carrier may be a sugar
alcohol such as mannitol or erythritol, and the particles may be
prepared by atomisation. The amount of water needs to be sufficient
to dissolve the sugar alcohol and is preferably at least 50% by
weight. This water needs to be driven off by heating with the
result that the water vapour generated by the heating creates pores
and channels as it is driven off These pores, which are visible
from the scanning electron microscopy images in FIGS. 2 and 5 of
this document, are certainly desirable for increasing the
solubility of poorly soluble pharmaceutical actives but are
definitely undesirable for effectively encapsulating volatile
actives since the latter would be able to escape through the pores.
It would thus be desirable to provide a delivery system having a
structure with reduced or minimised porosity.
[0028] It is an object of the present invention to address one or
more of the problems and/or to provide one or more of the solutions
mentioned above.
SUMMARY OF THE INVENTION
[0029] Accordingly, the present invention provides a spray-chilled
particulate delivery system, the particulate delivery system
comprising a crystalline structure and comprising (i) a carrier
material selected from the group consisting of erythritol and
mannitol and mixtures thereof, and (ii) a volatile hydrophobic
active ingredient that is liquid at wherein, relative to the total
weight of the carrier material, 75% or more of the carrier material
is in crystalline form.
[0030] The invention further provides a process for preparing a
particulate delivery system having a crystalline structure
comprising the steps of: [0031] (i) forming a melt of a carrier
material selected from the group consisting of erythritol and
mannitol and mixtures thereof, [0032] (ii) incorporating a volatile
hydrophobic active ingredient into the melt, [0033] (iii) forming a
melt-mixture comprising an emulsion, dispersion, solution or
suspension of the volatile hydrophobic active ingredient in the
melt, [0034] (iv) forming discrete particles of the melt mixture,
and [0035] (v) cooling the discrete particles, so as to form a
particulate delivery system in which, relative to the total weight
of the carrier material, 75% or more of the carrier material is in
crystalline form.
DETAILED DESCRIPTION
[0036] The delivery system of the present invention comprises a
carrier material selected from the group consisting of erythritol
and mannitol and mixtures thereof.
[0037] These materials have the technical common feature that they
are hydrophilic, non-polymeric, that they melt at below a
temperature of 190.degree. C. and that, upon solidification, they
crystallize rapidly. In this context "rapidly" means that the ratio
of the melting temperature of the erythritol and/or mannitol to the
glass transition temperature of the corresponding alcohol of
erythritol and/or mannitol is more than 1.7. That is, these
materials have a significantly higher propensity to form crystals
than to form amorphous masses, as is the case for the many sugar
alcohols that are unsuitable for use in the present invention.
[0038] The delivery system is crystalline. In the context of the
present invention, "crystalline" means that, relative to the total
weight of the carrier material, 75% or more, more preferably 80% or
more, most preferably 90% or more of the matrix or carrier material
is in crystalline form. This has the advantage that it is less
hygroscopic than, for instance, amorphous delivery systems.
[0039] By "in crystalline form" is meant that the matrix comprises
crystals that exhibits long-range order in three dimensions and/or
that the matrix comprises meso-crystals, as described in the
publication (12) Colfen, H.; Antonietti, M. Angew. Chem., Int. Ed.
2005, 44, 5576, i.e. a superstructure of crystalline nanoparticles
with external crystal faces on the scale of some hundred nanometres
to micrometers. Crystallinity and meso-crystallinity can be
measured using known techniques in the art such as powder x-ray
diffraction (PXRD) crystallography, scanning electron microscopy,
solid state NMR or differential scanning calorimetry (DSC).
[0040] The advantage of using a non-polymeric crystalline carrier
is that, upon spray-chilling, the carrier will tend to crystallise
such that all the molecules occupy defined spaces in the lattice.
By contrast, conventional polymeric carriers, such as polyethylene
glycol, tend to crystallize in regions along their length, leaving
the remainder of the polymer essentially amorphous.
[0041] Thus, without wishing to be bound by theory it is believed
that the delivery system of the present invention provides a
structure in which the active ingredient is not merely entrapped
between large crystals (such as macro or microscopic crystals), as
is the case in many conventional encapsulation systems, but is, to
an increased extent, included within crystals or meso-crystalline
domains.
[0042] By "included" it is meant that the active ingredient becomes
incorporated within a host crystal or meso-crystalline domain as a
molecule or droplet. This is in contrast to, for instance,
entrapment where the active is concentrated between crystal grain
boundaries.
[0043] The delivery system is spray-chilled. This provides the
advantage that the discrete particles have a reduced tendency to
form voids and shell-like structures, such as may occur during
conventional spray drying processes.
[0044] Further, spray-chilling typically provides a more
homogeneous particle size than, for instance, conventional spray
drying.
[0045] Therefore, a skilled person in the art will be able to
ascertain, by looking at the particles, a structural difference
from particles produced by other drying techniques.
[0046] The carrier materials are selected from the group consisting
of erythritol and mannitol and mixtures thereof. If the carrier
material comprises a mixture, it is preferred that erythritol forms
at least 70% by weight, more preferably 80%, most preferably 90% or
even 95% of the mixture in order to reduce the risk of lattice
substitution or phase separation during the crystallization step
and thereby reduce the risk of forming pores or channels through
which a volatile active ingredient would be lost. Most preferably,
the carrier is erythritol since it is a stable crystalline material
at room temperature and melts at a temperature of 121.degree. C.
Its viscosity, as measured by rotational viscometry, is only 24
mPas at 130.degree. C., which reduces the energy input required
during processing compared to more viscous materials and lowers the
associated risk of overheating the sensitive active ingredient. Its
rapid rate of crystallization also provides the benefit that the
creation of pores of channels in the delivery system during cooling
is significantly reduced.
[0047] The freely-settled bulk density of the product comprising
the particles of the invention is preferably from 0.7 g cm.sup.-3
to 1.35 g cm.sup.-3.
[0048] The particle density, i.e. the density of the individual
particles, is preferably from 1 g cm.sup.-3 to 1.45 g
cm.sup.-3.
[0049] The delivery system comprises an active ingredient. In the
context of the present invention, the phrase "active ingredient"
denotes an ingredient, component, mixture of ingredients or the
like that it is desired to encapsulate.
[0050] The active ingredient is hydrophobic. In the context of the
present invention the term "hydrophobic" means that, where the
active ingredient is a single compound, it has a ClogP greater than
2 and where the active ingredient is a mixture of compounds, 50% by
weight or more of the compounds have a ClogP higher than 2, more
preferably greater than 3. For the purposes of the present
invention, ClogP is measured using the ClogP calculator "EPI Suite
version 3, 2000 from the US Environmental Protection Agency.
[0051] The active ingredient is preferably present in an amount
ranging from about 5% to about 50% by weight, based on the total
weight of the delivery system.
[0052] It is critical that the active ingredient is hydrophobic
since this directly affects the nature of the spray-chilled product
and the effectiveness of the encapsulation. By contrast, it is not
critical whether the active ingredient is typically for use in, for
instance, the flavor and fragrance industry, the pharmaceutical
industry, the foods industry, or any other industry since the
technical domain does not have a bearing on the successful
encapsulation of the active ingredient in the form of a
spray-chilled particle.
[0053] In one aspect, the solubility of the carrier component, i.e.
erythritol, mannitol or mixtures thereof, in a solution of the
active ingredient may be less than 10% by weight of the total
carrier component at room temperature. If it is more soluble than
this then the risk that the delivery system does not form the
required crystalline structure is increased.
[0054] The active ingredient may be characterised by a Hildebrand
solubility parameter smaller than 30 [MPa.].sup.1/2. The aqueous
incompatibility of most oily liquids can be in fact expressed by
means of Hildebrand's solubility parameter .delta. which is
generally below 25 [MPa.].sup.1/2, while for water the same
parameter is of 48 [MPa].sup.1/2, and of 15-16 [MPa].sup.1/2 for
alkanes. This parameter provides a useful polarity scale correlated
to the cohesive energy density of molecules. For spontaneous mixing
to occur, the difference in .delta. of the molecules to be mixed
must be kept to a minimum. The Handbook of Solubility Parameters
(ed. A.F.M. Barton, CRC Press, Bocca Raton, 1991) gives a list of
.delta. values for many chemicals as well as recommended group
contribution methods allowing to calculate .delta. values for
complex chemical structures.
[0055] The hydrophobic active ingredient is liquid at 45.degree. C.
and 1 atmosphere. The delivery system of the present invention
provides an excellent protection against loss upon storage for such
liquid hydrophobic ingredients.
[0056] The liquid active ingredient may also be volatile. By
volatile, it is meant that the active ingredient has a vapour
pressure of .gtoreq.0.007 Pa at 25.degree. C. If the active
ingredient comprises a mixture of compounds, preferably at least 10
wt %, based on the total weight of the active ingredient, have a
vapour pressure of .gtoreq.0.1, more preferably at least 10 wt %
have a vapour pressure of .gtoreq.1 Pa at 25.degree. C., and most
preferably at least 10 wt % have a vapour pressure of .gtoreq.10 Pa
at 25.degree. C.
[0057] For the sake of example, the following non-exhaustive
categories of active ingredient are provided. Thus, for instance,
the active ingredient may be a flavoring, perfuming or
nutraceutical ingredient or composition.
[0058] The phrase "flavor or fragrance compound or composition" as
used herein, thus defines a variety of flavor and fragrance
materials of both natural and synthetic origin. They include single
compounds and mixtures. Natural extracts can also be encapsulated
in the extrudate; these include e.g. citrus extracts, such as
lemon, orange, lime, grapefruit or mandarin oils, or essential oils
of spices, amongst other.
[0059] The phrase flavor includes not only flavors that impart or
modify the smell of foods but include taste imparting or modifying
ingredients. The latter do not necessarily have a taste or smell
themselves but are capable of modifying the taste that other
ingredients provides, for instance, salt enhancing ingredients,
sweetness enhancing ingredients, umami enhancing ingredients,
bitterness blocking ingredients and so on.
[0060] Further specific examples of such flavor and perfume
components may be found in the current literature, e.g. in Perfume
and Flavor Chemicals, 1969, by S. Arctander, Montclair N.J. (USA);
Fenaroli's Handbook of Flavor Ingredients, CRC Press or Synthetic
Food Adjuncts by M. B. Jacobs, van Nostrand Co., Inc. They are
well-known to the person skilled in the art of perfuming, flavoring
and/or aromatizing consumer products, i.e. of imparting an odour or
taste to a consumer product.
[0061] An important class of oxygen-sensitive active materials that
can be encapsulated in the delivery system of the present invention
are "oils rich in polyunsaturated fatty acids", also referred to
herein as "oils rich in PUFA's". These include, but are not limited
to, oils of any different origins such as fish or algae. It is also
possible that these oils are enriched via different methods such as
molecular distillation, a process through which the concentration
of selected fatty acids may be increased. Particularly preferred
compositions for encapsulation are nutraceutical compositions
containing polyunsaturated fatty acids and esters thereof.
[0062] Specific oils rich in PUFA's for use in the present delivery
system include eicosapentanoic acid (EPA), docosahexanoic acid
(DHA), arachidonic acid (ARA), and a mixture of at least two
thereof.
[0063] Such oils may, optionally, be supplemented with an
antioxidant. For example, the antioxidant-supplemented oil may
comprise added ascorbic acid (vitamin C) and/or tocopherol (vitamin
E). Tocopherol may be .alpha.-, .gamma.-, or .delta.-tocopherol, or
mixtures including two or more of these, and is commercially
available. Tocopherols are soluble in oils and may be easily added
at amounts in the range of 0.05-2%, preferably 0.1-0.9%, of the
supplemented oil comprising the antioxidant.
[0064] The delivery system may comprise further optional
components. For instance, a carbohydrate such as a monosaccharide,
an oligosaccharide, a polysaccharide or any modified form thereof,
may be present. It is important that the carbohydrate is not
present at a level that would adversely affect the crystalline
structure of the delivery system. Thus, in the matrix, any such
carbohydrate is present at a level of 5% by weight or less.
[0065] An emulsifier may be present in the delivery system.
Examples of suitable emulsifiers include lecithin, modified
lecithins such as lyso-phospholipids, DATEM, mono- and diglycerides
of fatty acids, sucrose esters of fatty acids, citric acid esters
of fatty acids, and other suitable emulsifiers as cited in
reference texts such as Food Emulsifiers And Their Applications,
1997, edited by G. L. Hasenhuettl and R. W. Hartel.
[0066] A viscosity modifier may be present in the delivery system.
Examples of suitable viscosity modifiers include ethyl cellulose
(e.g. the Ethocel range from Dow Chemicals), hydrophobic silicas
and organophilic clay.
[0067] Water may be present at very low levels in the matrix. For
instance, 10% or less by weight based on the total weight of the
matrix, more preferably 7% or less, even more preferably 5% or
less, most preferably 2% or less, e.g. 1% or less by weight of
water may be present. Such a small amount of water may beneficially
lower the melting point of the crystal thereby reducing the
temperature to which the active ingredient is subjected.
Furthermore, since there is little or no need to remove water from
the mixture in preparing the spray-chilled particles, there is a
minimal risk of "puffing" due to the evaporation of water. This is
a known problem with spray-drying where the water, as it
evaporates, can create voids in the particle structure. Thus, the
spray-chilled particles of the invention typically have a higher
density than corresponding spray-dried particles and so provide for
a more compact storage and transportation of the finished
product.
[0068] Adjuvants such as food grade colorants can also be present
so as to provide colored delivery systems.
[0069] If desired, an anticaking agent can be present to reduce the
risk of the granules from sticking to one another.
[0070] The delivery system may be further encapsulated to provide
additional benefits. For instance, a barrier material may be coated
onto the delivery system, in order to serve as a moisture barrier
or an enteric coating. Examples of suitable barrier materials
include modified celluloses such as ethyl cellulose, waxes, fats,
zein, shellac and the like.
[0071] The delivery system according to the present invention
comprises particles. The particles can comprise individual crystals
or a plurality of crystals. For instance, the particles of the
delivery system may comprise a lattice of crystals joined together.
Preferably the average particle size, based on the mean diameter,
of the granules is from 50 to 4000 microns. The particles are
preferably of substantially uniform granulometry.
[0072] The process of the invention comprises distinct steps:
(i) Forming a Melt of a Carrier Material Selected from the Group
Consisting of Erythritol and Mannitol and Mixtures Thereof
[0073] This forms a liquid from the continuous phase which is
essential so that the flavor or fragrance can be emulsified or
dispersed within it.
[0074] It is highly desirable that the melting point of the
continuous phase is less than 190.degree. C. since this helps to
prevent significant degradation of heat labile active ingredients.
It is further important to carry out the process at a temperature
below the flash point of the active ingredient so that the vapour
pressure of the active ingredient is maintained at an acceptably
low level.
(ii) Incorporating a Volatile Hydrophobic Active Ingredient into
the Melt
[0075] This step can be performed by any standard process and the
skilled person will readily appreciate suitable methods by which
this can be accomplished.
(iii) Forming a Melt-Mixture Comprising an Emulsion, Dispersion, or
Suspension of the Melt
[0076] Preferably the emulsion, dispersion or suspension is formed
under conditions in which the product is homogenized.
Homogenization is highly advantageous since it reduces the risk of
phase separation which, upon solidification, would cause the active
ingredient not to be included within the crystalline structure of
the carrier material.
[0077] Optionally and advantageously, the melt mixture is
supercooled. In other words, it is preferably cooled below the
melting point of the matrix material but remains in the form of a
melt. This allows for the reduction in the vapor pressure of the
active ingredient and reduces the amount of heat energy that needs
to be removed in the subsequent step.
[0078] If an emulsion is formed from the melt, it is preferred that
the phase volume of the oil is less than 50%, more preferably less
than 40% so as to maintain the emulsion with the oil in the
dispersed phase of the emulsion.
[0079] The melt-mixture comprises a low amount of water, enabling
the formation of the spray-chilled solid without requiring a large
amount of water to be driven off. Thus the melt-mixture comprises
10% or less, more preferably 7% or less, even more preferably 5% or
less, most preferably 2% or less, e.g. 1% or less by weight of
water by weight based on the total weight of the melt-mixture.
(iv) Forming Discrete Particles of the Melt-Mixture
[0080] In the context of the present invention, "discrete
particles" means particles, droplets or fibres.
[0081] The particles are preferably formed by a process that is
suitable for low viscosity melts. For instance, the particles may
be formed by techniques such as ultrasonic atomization, centrifugal
whell atomization, prilling (break-up of a jet or dripping).
[0082] Cutting or chopping is not suitable in the present context
since this typically requires high viscosity melts in order to be
effective.
[0083] Grinding is especially unsuitable since this exposes
significantly more of the active ingredient to the atmosphere and
thus, in the case of volatile active ingredients, leads to the loss
of excessive amounts thereof
[0084] Thus, the step of forming discrete particles preferably does
not consist of cutting, chopping or grinding.
[0085] The formation is carried out on the melt either above the
melt temperature of the matrix or, more preferably, on the
supercooled matrix.
[0086] Any suitable commercially available apparatus known to the
skilled person can be used in this step.
[0087] The formation of discrete particles whilst the mixture is in
the form of a melt is essential since the minimises the loss of
active ingredient from the delivery system, especially when
compared to known delivery systems that rely on crushing or
grinding a solidified mass to form granules and which allow the
loss of active ingredient that is at the surface of the particles
where it is ground.
(v) Cooling the Discrete Particles
[0088] Cooling of the melt particles formed in the previous step is
required to induce crystallisation.
[0089] The cooling step is performed rapidly in order to ensure
that the active ingredient remains included, to a significant
extent, in the developing crystals. For instance, it is desirable
that the cooling step comprises heat removal at a rate of greater
than about 600 kJ.kg.sup.-1.min.sup.-1.
[0090] This is advantageous in that it allows the active ingredient
to be encapsulated to a greater extent within the developing
crystals, resulting in excellent barrier properties upon
storage.
[0091] To achieve the rapid cooling required according to the
present invention, suitable processes include, but are not limited
to spray congealing, spray chilling, or melt atomization. Such
processes are sometimes referred to generically as prilling. The
cooling step can be performed by quenching with a cooling medium,
such as a cooling gas or liquid, Inert gases and liquids such as
limonene, liquid nitrogen, cooling media air, nitrogen and carbon
dioxide are all suitable for this purpose.
[0092] Suitable apparatus and processes include cooling of the
particles in a cooling tower, fluidized bed or cooled belt or
directly in an immiscible fluid.
[0093] In the process according to the present invention, the
incorporation of the volatile hydrophobic active ingredient, the
formation of the discrete particles, and the crystallization
processes are achieved in distinct phases or steps of the process.
This is in contrast to traditional co-crystallization processes for
forming crystalline delivery systems, which involves volatilization
of water at the same time as oil incorporation. Such differences
provide the process of the present invention with a more precise
control of the nature of the delivery system and reduce the risk of
creating channels in the crystalline structure that are a known
factor contributing to a porous network by which volatile active
ingredients can escape upon storage.
[0094] In the process according to the present invention, there is
little or no reduction in moisture content during any of the steps.
This allows for a more effective inclusion and entrapment of the
active and thereby allows improved protection against
oxidation.
[0095] Further, the delivery system is not subject to a drying step
using heat, such as in a spray-drying process, which is often a
principle cause of the loss of volatile, hydrophobic active
ingredient.
[0096] The delivery system can be used to enhance a variety of
products. For instance, it can be used in edible compositions such
as foodstuffs, pharmaceutical compositions, nutraceutical
compositions, oral care compositions, such as chewing-gum or
toothpaste, as well as home-care and body-care compositions.
[0097] For instance, non-limiting examples where the delivery
system finds utility include dry beverages, dry doughs such as cake
or bread mixes, cookies, intermediate moisture content foods, stock
cubes, powdered laundry detergents, pharmaceutical tablets.
[0098] In the case of drug delivery systems, the delivery system of
the present invention is particularly useful as it will ensure
similar composition and release properties from batch to batch.
[0099] If the active ingredient is a flavor oil, it can be
advantageously used to impart or modify the organoleptic properties
of a great variety of edible products, i.e. foods, beverages,
pharmaceuticals and the like. In a general manner, they enhance the
typical organoleptic effect of the corresponding unencapsulated
flavor material.
[0100] Where the active material is an oil rich in polyunsaturated
fatty acids or a nutraceutical composition comprising such an oil,
it can be provided in any foodstuff where health benefits are
desired. In such products, a further advantage of the present
delivery system is that it can mask the flavor of the oil rich in
polyunsaturated fatty acids, which may not be compatible with the
flavor of the foodstuff into which it is incorporated.
[0101] The total amount of delivery system in such consumer
products can vary across a wide range of values, which are
dependent on the nature of the consumer product and that of the
particular delivery system of the invention used.
[0102] Typical amounts, to be taken strictly by way of example, are
comprised in a range of values as wide as from 0.001% to 5 or even
10% of the weight of a flavoring composition or finished consumer
product into which they are included.
EXAMPLES
[0103] The invention will now be described in further detail by way
of the following examples.
Example 1
Preparation of a Delivery System of the Invention
[0104] A mixture of 9 parts molten erythritol and 1 part of a
limonene/lecithin solution (9 parts limonene to 1 part lecithin)
were poured into a pressurizable vessel and tempered to 130.degree.
C. The two fluids were then mixed for 30 seconds using an Ultra
Turrax homogenizer to create an emulsion. This emulsion was pushed
through a spray nozzle under 60 psi of nitrogen head pressure. The
spray broke up into fine melt-emulsion droplets, which then fell
onto a room temperature metal tray. Within seconds the droplets
hardened forming crystallized solid granules of erythritol
containing the dispersed limonene. Photomicrographs of the granules
were taken and showed the oil droplets primarily within the
erythritol crystals. The granules had a dense structure and a fine
particle size <850 .mu.m.
[0105] The amount of active ingredients (limonene and lecithin)
retained within the granules was measured by low-field time-domain
nuclear magnetic resonance (LF-TD-NMR) as described by Aeberhardt
(Food Biophysics 3, 1, 33-48 2008). A Bruker Optics Minispec 20 MHz
spectrometer was used to measure 4 scans of the
90.degree./180.degree. spin-echo signal with a 3.5 ms delay time,
0.5 ms acquisition window and a 20 second recycle delay. The
spin-echo signal was proportional to the mass of the
limonene/lecithin solution in the sample. After calibrating the
system using carefully measured mixtures of a limonene/lecithin
solution and as-received erythritol, the active ingredient content
of the granules was found to be 9.57 wt %. Thus 95.7% of the active
ingredients were retained within the granules.
Example 2
Preparation of a Further Delivery System of the Invention
[0106] A mixture of 9 parts molten erythritol and 1 part of a
limonene/lecithin solution (9 parts limonene to 1 part lecithin)
was prepared and sprayed to form melt emulsion droplets as in
Example 1. The spray was then allowed to fall into a 5cm deep
agitated bath of limonene at 0.degree. C.
[0107] The sprayed droplets hardened sufficiently fast to avoid
coalescence in the bath. The hardened particles were collected and
allowed to air dry on a paper towel in order to remove limonene
from the surface. The resulting powder was composed of dense
particles and contained 9.01 wt % active ingredients (90.1%
retention) based on LF-TD-NMR measurements.
Example 3
Preparation of a Comparative Delivery System
[0108] Following the same method used in example 2, a mixture of 9
parts molten sorbitol and 1 part of a limonene/lecithin solution (9
parts limonene to 1 part lecithin) was prepared and sprayed to form
melt emulsion droplets which were then allowed to fall into a 5 cm
deep agitated bath of limonene at 0.degree. C. However, the
droplets coalesced and reformed a single viscous mass at the bottom
of the bath. The quench fluid was decanted and the mass was allowed
to sit unperturbed at room temperature. After one week, the mass
remained soft and could not be milled to form particles.
Example 4
Preparation of a Further Comparative Delivery System
[0109] Following the same method used in example 2, a mixture of 9
parts molten xylitol and 1 part of a limonene/lecithin solution (9
parts limonene to 1 part lecithin) was prepared and sprayed to form
melt emulsion droplets similarly according to the same method used
in examples 1 and 2. The spray was then allowed to fall into a 5cm
deep agitated bath of limonene at 0.degree. C. However, the
droplets coalesced and reformed a single viscous mass at the bottom
of the bath. The quench fluid was decanted and the mass was allowed
to sit unperturbed at room temperature. Within 24 hours the mass
had hardened sufficiently to permit milling. Particle size was
reduced using a mortar and pestle until the material passed through
a U.S. Standard Sieve Series #20 sieve. The resulting powder had a
wetted or agglomerated appearance, indicating liberation of the
liquid active ingredients. After air-drying on a paper towel to
allow limonene remaining on the surface of the particles to
evaporate off, the liquid content of the powder was measured by
TD-LF-NMR. The active ingredient content was found to be 0.48 wt %
(4.8% retention).
Example 5
[0110] Preparation of a Further Delivery System according to the
Invention
[0111] A mixture of 9 parts molten erythritol and 1 part of a mint
flavour (ex Firmenich, Geneva, Switzerland, reference 885106
NT)/lecithin solution (9 parts mint to 1 part lecithin) was poured
into a pressurizable vessel and tempered to 130.degree. C. The two
fluids were then mixed for 30 seconds using a Ultra Turrax T25
homogenizer (IKA Works, to create an emulsion. This emulsion was
pushed through a 22 gauge needle under 20 psi of nitrogen head
pressure forming a liquid jet. After falling a distance of 0.5 m
the jet broke up into droplets, which in turn fell into a 25 cm
deep beaker of limonene chilled to 0.degree. C. The droplets
hardened sufficiently fast to avoid coalescence at the bottom of
the beaker. The hardened prills were collected and allowed to air
dry on a paper towel in order to remove limonene from the surface.
This process yielded solid granules.
[0112] Measurements by LF-TD-NMR that were calibrated using
measured mixtures of as-received erythritol and mint
flavour/lecithin solutions, showed that the droplets contained 9.12
wt % active ingredients (91.2% of the active ingredients were
retained).
Example 6
[0113] Flavored Chewing Gums with Iso-Loading of Flavor
[0114] An unflavored chewing gum base was prepared having the
following ingredients in the amounts shown.
TABLE-US-00001 TABLE 1 Ingredient Amount (wt %) Solsona T Gum Base
(1) 12.44 Vega Gum Base (1) 12.44 Crystalline sorbitol P60W 56.50
Maltitol Syrup 11.50 Glycerin 6.92 Aspartame 0.12 Acesulfame K 0.08
(1) ex Cafosa
[0115] A Sigma-blade mixer was pre-heated to 45.degree.
C.-50.degree. C. and half of the polyols were added. The gum base
was pre-heated to 60.degree. C.-65.degree. C. and added to the
mixer. Mixing was carried out for approximately 4 minutes. Next,
the remaining polyols, sweeteners and humectants were added and
mixing continued for 4 minutes.
[0116] The unflavored chewing gum base prepared above was then
flavored to provide the following iso-load chewing gum
compositions:
TABLE-US-00002 TABLE 2 Component Sample 1 (CONTROL) Sample 2 (TEST)
Unflavored Chewing Gum 99.70 96.67 Liquid Mint Flavor (1) 0.30 --
Mint Encapsulated -- 3.33 Flavor (2) (1) ex Firmenich, Geneva,
Switzerland (reference 885106 NT) (2) prepared in example 5
[0117] For the both samples the flavor/encapsulated flavor was
added and mixing was continued for 2 minutes. The flavored chewing
gum was then discharged, laminated and cut into sticks or
slabs.
[0118] 6 trained panellists assessed each chewing gum sample for
flavor intensity as follows:
[0119] Samples were presented blind and following a balanced
presentation order. The flavor intensity was evaluated on a scale
of 0 to 10 where 0 denotes no flavor and 10 denotes very strong
flavor. All panellists found sample 2 significantly stronger than
sample 1, with extremely intense impact of mint flavor and stronger
mentholic and cooling character.
Example 7
[0120] Flavored Chewing Gums with Iso-Dosage of Capsule to Liquid
Flavor
[0121] Unflavored chewing gum was prepared as described in example
6 and was then flavored to provide the following iso-dosage chewing
gum compositions:
TABLE-US-00003 TABLE 3 Component Sample 1 (CONTROL) Sample 3 (TEST)
Unflavored Chewing Gum 99.70 99.70 Liquid Mint Flavor (1) 0.30 --
Mint Encapsulated -- 0.30 Flavor (2) (1) ex Firmenich, Geneva,
Switzerland (reference 885106 NT) (2) prepared in example 5
[0122] For both samples, the flavor or encapsulated flavor was
added and mixing continued for 2 minutes. The flavored chewing gum
was discharged, laminated and cut into sticks or slabs.
[0123] 6 trained panellists assessed each chewing gum sample for
flavor intensity as follows.
[0124] Samples were presented blind and following a balanced
presentation order. The flavor intensity was evaluated on a scale
of 0 to 10 where 0 denotes no flavor or and 10 denotes very strong
flavor. All panellists found sample 3 stronger than sample 1
(control), with significantly higher impact of mint flavor.
Example 8
[0125] Flavored Chewing Gums with Iso-Loading of
Flavour--Comparison between Spray-Chilled and Spray-Dried
[0126] Unflavored chewing gum was prepared as described in example
6 and was then flavored to provide the following iso-flavor load
chewing gum compositions:
TABLE-US-00004 TABLE 4 Component Sample 4 (CONTROL) Sample 5 (TEST)
Unflavored Chewing Gum 98.27 96.87 Mint Flavor - Spray-dry (1) 1.73
-- Mint Encapsulated -- 3.13 Flavor (2) (1) ex Firmenich, Geneva,
Switzerland (reference 505951 TP0504 containing liquid mint flavor
885106NT - 14.45% loading of mint liquid flavor) (2) prepared
according to the process of example 5 (7.99% loading of mint liquid
flavor)
[0127] For both samples, the encapsulated flavor was added and
mixing continued for 2 minutes. The flavored chewing gums were then
discharged, laminated and cut into sticks or slabs. Encapsulated
samples 4 and 5 contained iso-load of mint liquid flavour, as
confirmed by NMR.
[0128] Taste evaluation of samples 4 and 5 was then performed as
follows: 6 trained panellists assessed each chewing gum sample for
flavor intensity after chewing for 30 seconds, 1 minute and 3
minutes. Samples were presented blind and following a balanced
presentation order. The flavor intensity was evaluated on a scale
of 0 to 10 where 0 denotes no flavor or and 10 denotes very strong
flavor. The results are given in the following table.
TABLE-US-00005 TABLE 5 30 seconds 1 minute 3 minutes (Average of
(Average of (Average of Sample panellist scores) panellist scores)
panellist scores) 4 (control) 4 3.6 2.3 5 (test) 7.6 5.7 3.1
[0129] All panellists found sample 5 significantly stronger than
sample 4, with significantly higher impact of mint flavour.
* * * * *